Staphylococcus aureus-derived lipoteichoic acid induces temporary T-cell paralysis independent of Toll-like receptor 2

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:138

Article

Kaesler, Susanne^1,2  Skabytska, Yuliya¹  Chen, Ko-Ming^1,6  Kempf, Wolfgang E.^1,2  Volz, Thomas^1,2  Koeberle, Martin^1,2  Woelbing, Florian^1,2  Hein, Ulrike¹  Hartung, Thomas^3,4  Kirschning, Carsten⁵  Roecken, Martin¹  Biedermann, Tilo^1,2 

[1] Eberhard Karls Univ Tubingen, Dept Dermatol, Liebermeisterstr, Tubingen, Germany

[2] Tech Univ Munich, Dept Dermatol & Allergol, Biedersteinerstr 29, D-80802 Munich, Germany

[3] Univ Konstanz, Ctr Alternat Anim Testing Europe, Constance, Germany

[4] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA

[5] Univ Duisburg Essen, Inst Med Microbiol, Essen, Germany

[6] Derma Lab Dusseldorf, Dusseldorf, Germany

关键词: Lipoteichoic acid;    T cell;    temporary unresponsiveness;    Staphylococcus aureus;    atopic dermatitis;    cell cycle;   

DOI  :  10.1016/j.jaci.2015.11.043

来源: Elsevier

【 摘 要 】

Background: The interplay between microbes and surface organs, such as the skin, shapes a complex immune system with several checks and balances. The first-line defense is mediated by innate immune pathways leading to inflammation. In the second phase specific T cells invade the infected organ, amplifying inflammation and defense. Consecutively, termination of inflammation is crucial to avoid chronic inflammation triggered by microbes, such as in patients with atopic dermatitis. Objective: We aimed to elucidate how the Staphylococcus aureus-derived cell-wall component lipoteichoic acid (LTA) governs the second phase of immune responses when high concentrations of LTA access T cells directly through disrupted skin. Methods: We analyzed the direct exposure of T cells to LTA in vitro. For in vivo analyses, we used fluorescein isothiocyanate contact hypersensitivity and ovalbumin-induced dermatitis as models for T(H)2-mediated cutaneous inflammation. Results: We observed that LTA potently suppressed Tlymphocyte activation in a Toll-like receptor 2-independent manner. LTA-exposed T cells did not proliferate and did not produce cytokines. Importantly, these T cells remained completely viable and were responsive to consecutive activation signals on subsequent removal of LTA. Thus LTA exposure resulted in temporary functional T-cell paralysis. In vivo experiments revealed that T-cell cytokine production and cutaneous recall responses were significantly suppressed by LTA. Conclusion: We identified a new mechanism through which bacterial compounds directly but temporarily modulate adaptive immune responses.

【 授权许可】

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